The overall objective of the project is to examine the possibility that the primary biochemical lesion in muscular dystrophy is manifested as a generalized defect in cell membranes. If such a defect does, in fact, occur, membrane alterations seen in skeletal muscle should also be observable in other cell types exhibiting similar functions. Thus we propose to evaluate the effects of muscular dystrophy on membrane events associated with a physiological function common to skeletal muscle and to brown adipocytes. This physiological function -- nonshivering heat production -- has already been shown by us to be altered in the intact, dystrophic hamster. The membrane events to be evaluated are those involved with recognition of the extracellular signal carried to the target cell by norepinephrine and the recoding of this signal to an intracellular message able to stimulate substrate oxidation (and therefore heat production). Specifically, we plan to examine in both skeletal muscle and brown adipocytes the adrenergic-induced changes in membrane potentials and membrane resistances using microelectrodes for the intracellular recordings. These will be measured on intact hamster cells, in vivo or in vitro, and will involve experiments to determine the magnitude of the effect of the myopathy as well as the type of adrenergic pathway involved in the altered response. In addition, the effectiveness of adrenergic stimulation, in terms of rates of nonshivering heat production, will be assessed by measuring rates of oxygen consumption for isolated brown adipocytes (manometrically) and single skeletal muscle cells (using a p02 electrode). Finally, the number of Beta-adrenergic receptors on the membranes of both cell types will be estimated to determine the effect of the myopathy on receptor distribution. The experiments of the proposed study should provide insight into the nature and generality of the membrane alterations in muscular dystrophy as well as providing information regarding the regulation of nonshivering thermogenesis in skeletal muscle.